title: Interactive effect of STAT6 and IL13 gene polymorphisms on eczema status: results from a longitudinal and a cross-sectional study.
abstract: BACKGROUND
  Eczema is a prevalent skin disease that is mainly characterized by systemic deviation of immune response and defective epidermal barrier. Th2 cytokines, such as IL-13 and transcription factor STAT6 are key elements in the inflammatory response that characterize allergic disorders, including eczema. Previous genetic association studies showed inconsistent results for the association of single nucleotide polymorphisms (SNPs) with eczema. Our aim was to investigate whether SNPs in IL13 and STAT6 genes, which share a biological pathway, have an interactive effect on eczema risk.
  
  
  METHODS
  Data from two independent population-based studies were analyzed, namely the Isle of Wight birth cohort study (IOW; n = 1,456) and for the purpose of replication the Swansea PAPA (Poblogaeth Asthma Prifysgol Abertawe; n = 1,445) cross-sectional study. Log-binomial regressions were applied to (i) account for the interaction between IL13 (rs20541) and STAT6 (rs1059513) polymorphisms and (ii) estimate the combined effect, in terms of risk ratios (RRs), of both risk factors on the risk of eczema.
  
  
  RESULTS
  Under a dominant genetic model, the interaction term [IL13 (rs20541) × STAT6 (rs1059513)] was statistically significant in both studies (IOW: adjusted P(interaction) = 0.046; PAPA: P(interaction) = 0.037). The assessment of the combined effect associated with having risk genotypes in both SNPs yielded a 1.52-fold increased risk of eczema in the IOW study (95% confidence interval (CI): 1.05 - 2.20; P = 0.028) and a 2.01-fold higher risk of eczema (95% CI: 1.29 - 3.12; P = 0.002) in the PAPA study population.
  
  
  CONCLUSIONS
  Our study adds to the current knowledge of genetic susceptibility by demonstrating for the first time an interactive effect between SNPs in IL13 (rs20541) and STAT6 (rs1059513) on the occurrence of eczema in two independent samples. Findings of this report further support the emerging evidence that points toward the existence of genetic effects that occur via complex networks involving gene-gene interactions (epistasis).
authors.affiliation: Department of Epidemiology and Biostatistics, Norman J. Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, USA.
authors.forename: Ali H
authors.initials: AH
authors.lastname: Ziyab
authors.forename: Gwyneth A
authors.initials: GA
authors.lastname: Davies
authors.forename: Susan
authors.initials: S
authors.lastname: Ewart
authors.forename: Julian M
authors.initials: JM
authors.lastname: Hopkin
authors.forename: Eric M
authors.initials: EM
authors.lastname: Schauberger
authors.forename: Marsha
authors.initials: M
authors.lastname: Wills-Karp
authors.forename: John W
authors.initials: JW
authors.lastname: Holloway
authors.forename: Syed Hasan
authors.initials: SH
authors.lastname: Arshad
authors.forename: Hongmei
authors.initials: H
authors.lastname: Zhang
authors.forename: Wilfried
authors.initials: W
authors.lastname: Karmaus
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004485:Eczema / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018793:Interleukin-13 / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D050800:STAT6 Transcription Factor / Q000235:genetics*; D055815:Young Adult
chemical_list: D018793:Interleukin-13; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human